Contact, Collaboration, and Conflict: Signal Integration of Syk-Coupled C-Type Lectin Receptors

Abstract

conducted on CLR assigned to the so-called Dectin-1 or Dectin-2 clusters, localized within 51 the NK cell gene cluster on human chromosome 12 or mouse chromosome 6 (1-3). Several 52 excellent reviews on the function of these CLR in anti-microbial defense and homeostasis are 53 available (4, 5). In this review we summarize the current knowledge about signaling 54 downstream of the activating CLR Dectin-1 (Clec7a), Dectin-2 (human Clec6a, mouse 55 Clec4n), Mincle (Clec4e) and Mcl (Clec4d) that is largely dependent on the kinase spleen 56 tyrosine kinase (Syk). Table I provides an overview of defined ligands and microorganisms 57 bound by this group of PRR. In addition to microbial carbohydrate and glycolipid structures 58 acting as PAMP, several CLR bind endogenous ligands such as SAP130 released by dying 59 cells or cholesterol crystals. Thus, these CLR are involved in homeostatic responses and 60 inflammatory conditions (6-9), in addition to host response to pathogens and commensals (10-61 (Fig. 1). 103 Syk-Card9 coupled CLR is observed across cell-types and species, promoting the 111 differentiation of IL-17-producing CD4+ T cells (23, 24, 26, 27). Remarkably, to date there is 112 only very limited information about the effects of combined stimulation of CLR and TLR 113 pathways on global gene expression. 114

Macrophage Inducible C-Type Lectin As a Multifunctional Player in Immunity

“…(5)]. However, recent reports indicate that Mincle rather than purely inducing pro-inflammatory responses is an immune modulator as its engagement also promotes expression of anti-inflammatory cytokines and counter regulates pro-inflammatory signaling pathways (62). …”

CD209a Synergizes with Dectin-2 and Mincle to Drive Severe Th17 Cell-Mediated Schistosome Egg-Induced Immunopathology

“…Since cross talk between distinct classes of PRRs has the potential to diversify the innate immune responses of the host following microbial challenge (reviewed in Tan et al 2014), we postulated that CD209a could synergize with Dectin-2 to drive the inflammatory immune responses initiated by schistosomes in the high-pathology CBA strain. Receptor collaborations among TLRs and CLRs have been amply demonstrated (Ostrop and Lang, 2017). Within the Dectin-2 family, receptor heterodimerization (e.g., between Dectin-2 and Mincle) has been suggested to increase ligand binding and to enhance immune responses (Zhu et al, 2013).…”

Antifungal Innate Immunity: A Perspective from the Last 10 Years

“…All the receptors of this family couple with the ITAM-containing Fc receptor γ-chain (FcRγ) chain to drive intracellular signaling via the Syk-CARD9 pathway [27]. Signaling through these receptors can often synergize or antagonize that of other CLRs, including dectin-1, TLRs, and inflammasomes [28].…”

“…Other interactions between CLRs and TLRs have also been described, including dectin-1 and TLR2 crosstalk in the recognition and phagocytosis of zymosan, and their ability to synergize in the activation of NF-κB and subsequent cytokine production (Fig. 2) [27]. …”